Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.

Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6) to block cell cycle progression have been effective in treating hormone receptor-positive breast cancer, but triple-negative breast cancer (TNBC) remains largely resistant, limiting their clinical applicability. The study reveals that transcription regulator cyclin-dependent kinase7 (CDK7) is a promising target to circumvent TNBC's inherent resistance to CDK4/6 inhibitors. Combining CDK4/6 and CDK7 inhibitors significantly enhances therapeutic effectiveness, leading to a marked decrease in cholesterol biosynthesis within cells.

Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns.

Aims: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT.

Methods: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.

Spermatid perinuclear RNA-binding protein promotes UBR5-mediated proteolysis of Dicer to accelerate triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer with no targeted therapy. Spermatid perinuclear RNA binding protein (STRBP), a poorly characterized RNA-binding protein (RBP), has an essential role in normal spermatogenesis and sperm function, but whether and how its dysregulation contributing to cancer progression has not yet been explored. Here, we report that STRBP functions as a novel oncogene to drive TNBC progression.

Destabilization of microrchidia family CW-type zinc finger 2 via the cyclin-dependent kinase 1-chaperone-mediated autophagy pathway promotes mitotic arrest and enhances cancer cellular sensitivity to microtubule-targeting agents.

Background: Microtubule-targeing agents (MTAs), such as paclitaxel (PTX) and vincristine (VCR), kill cancer cells through activtion of the spindle assembly checkpoint (SAC) and induction of mitotic arrest, but the development of resistance poses significant clinical challenges.

Methods: Immunoblotting and RT-qPCR were used to investigate potential function and related mechanism of MORC2. Flow cytometry analyses were carried out to determine cell cycle distribution and apoptosis.

Dynamic SUMOylation of MORC2 orchestrates chromatin remodelling and DNA repair in response to DNA damage and drives chemoresistance in breast cancer.

SUMOylation regulates a plethora of biological processes, and its inhibitors are currently under investigation in clinical trials as anticancer agents. Thus, identifying new targets with site-specific SUMOylation and defining their biological functions will not only provide new mechanistic insights into the SUMOylation signaling but also open an avenue for developing new strategy for cancer therapy. MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme with an emerging role in the DNA damage response (DDR), but its regulatory mechanism remains enigmatic.

Protein Phosphatase 1 Subunit PPP1R14B Stabilizes STMN1 to Promote Progression and Paclitaxel Resistance in Triple-Negative Breast Cancer.

Unlabelled: Triple-negative breast cancer (TNBC) represents the most lethal subtype of breast cancer due to its aggressive clinical features and the lack of effective therapeutic targets. To identify novel approaches for targeting TNBC, we examined the role of protein phosphatases in TNBC progression and chemoresistance. Protein phosphatase 1 regulatory subunit 14B (PPP1R14B), a poorly defined member of the protein phosphatase 1 regulatory subunits, was aberrantly upregulated in TNBC tissues and predicted poor prognosis.

HSP90 N-terminal inhibitors target oncoprotein MORC2 for autophagic degradation and suppress MORC2-driven breast cancer progression.

Aims: MORC family CW-type zinc finger 2 (MORC2), a GHKL-type ATPase, is aberrantly upregulated in multiple types of human tumors with profound effects on cancer aggressiveness, therapeutic resistance, and clinical outcome, thus making it an attractive drug target for anticancer therapy. However, the antagonists of MORC2 have not yet been documented.

Methods And Results: We report that MORC2 is a relatively stable protein, and the N-terminal homodimerization but not ATP binding and hydrolysis is crucial for its stability through immunoblotting analysis and Quantitative real-time PCR.

Overexpression of Long Non-Coding RNA Linc01315 Predicts Poor Prognosis in Breast Cancer.

Background: LncRNAs have been shown to play critical roles in regulating tumorigenesis and tumor progression. Using LncRNAs to predict prognosis and therapeutic response to cancer treatment has been caused for concern, but the predictive value of lncRNAs remains to be explored and underlying mechanisms have not been completely understood.

Methods: The Linc01315 expression level was detected in 282 breast cancer tissues by using quantitative RT-PCR.

The Biological Function of TUSC7/miR-1224-3p Axis in Triple-Negative Breast Cancer.

Background: Triple-negative breast cancers (TNBC), comprising about 20% of breast cancers, have a poor prognosis. Currently, there is no effective target therapy for TNBC. LncRNA TUSC7 has been identified as a tumor suppressor in osteosarcoma and colorectal cancer.

TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer.

Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). Breast tumor-initiating cells (BTICs) are involved in forming VM; however, the specific VM-forming BTIC population and the regulatory mechanisms remain undefined. We find that tumor endothelial marker 8 (TEM8) is abundantly expressed in TNBC and serves as a marker for VM-forming BTICs.

Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE).

Purpose: Many patients with HR+, HER2- early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients with high-risk clinical and/or pathologic features may experience distant recurrence, many in the first few years. Superior treatment options are needed to prevent early recurrence and development of metastases for this group of patients.

Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis.

: Chromodomain Y-like 2 (CDYL2) is a member of the CDY gene family involved in spermatogenesis, but its role in human cancer has not been reported. Analyses of publicly available databases demonstrate that CDYL2 is abundantly expressed in breast tumors. However, whether CDYL2 is involved in breast cancer progression remains unknown.

Acetylation of MORC2 by NAT10 regulates cell-cycle checkpoint control and resistance to DNA-damaging chemotherapy and radiotherapy in breast cancer.

MORC family CW-type zinc finger 2 (MORC2) is an oncogenic chromatin-remodeling enzyme with an emerging role in DNA repair. Here, we report a novel function for MORC2 in cell-cycle checkpoint control through an acetylation-dependent mechanism. MORC2 is acetylated by the acetyltransferase NAT10 at lysine 767 (K767Ac) and this process is counteracted by the deacetylase SIRT2 under unperturbed conditions.

Neoadjuvant therapy and sentinel lymph node biopsy in HER2-positive breast cancer patients: results from the PEONY trial.

Objective: The aim of the study is to evaluate the optimal timing of sentinel lymph node biopsy (SLNB) in patients with clinical negative axillary lymph nodes (ALNs) before neoadjuvant therapy (NAT) and the feasibility of SLNB substituting for ALN dissection in patients with positive ALNs who convert to node negative, for HER2-positive disease.

Methods: Patients receiving SLNB with dual tracer mapping in the PEONY trial were analyzed.

Results: For 80 patients with clinical negative ALNs, the node negative rate by pathology after NAT was 83.

RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation of stability and oncogenic functions of HSPA2.

Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was  downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo.

Detection of breast cancer stem cell gene mutations in circulating free DNA during the evolution of metastases.

Purpose: Limited knowledge exists on the detection of breast cancer stem cell (BCSC)-related mutations in circulating free DNA (cfDNA) from patients with advanced cancers. Identification of new cancer biomarkers may allow for earlier detection of disease progression and treatment strategy modifications.

Methods: We conducted a prospective study to determine the feasibility and prognostic utility of droplet digital polymerase chain reaction (ddPCR)-based BCSC gene mutation analysis of cfDNA in patients with breast cancer.

Evaluating the effect of Avastin on breast cancer angiogenesis using synchrotron radiation.

Background: The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult.

Methods: To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology.

Survival and chemotherapy-related risk of second primary malignancy in breast cancer patients: a SEER-based study.

Background: With the improvement in the survival of breast cancer, developing second primary malignancy becomes a serious health issue. The aim of this study was to explore the survival of breast cancer patients with second primary malignancy, and to evaluate the impact of chemotherapy on the risk of different cancer sites.

Method: Obtaining data from the Surveillance, Epidemiology, and End Results database, we calculated the standardized incidence ratio (SIR) for second primary malignancy in breast cancer survivors between 2000 and 2014.

Association between breast cancer and thyroid cancer: A study based on 13 978 patients with breast cancer.

Background: Thyroid cancer (TC) is one of the most commonly seen secondary malignancy in breast cancer (BC) survivors.

Materials And Methods: A retrospective study was conducted in BC patients in our center from 1999 to 2013. Patients were divided into BC-TC group and BC-alone group.

FBXO22 Possesses Both Protumorigenic and Antimetastatic Roles in Breast Cancer Progression.

The molecular underpinnings behind malignant progression of breast cancer from a localized lesion to an invasive and ultimately metastatic disease are incompletely understood. Here, we report that F-box only protein 22 (FBXO22) plays a dual role in mammary tumorigenesis and metastasis. FBXO22 was upregulated in primary breast tumors and promoted cell proliferation and colony formation and xenograft tumorigenicity Surprisingly, FBXO22 suppressed epithelial-mesenchymal transition (EMT), cell motility, and invasiveness and metastatic lung colonization Clinical data showed that expression levels of FBXO22 were associated with favorable clinical outcomes, supporting the notion that metastasis, rather than primary cancer, is the major determinant of the mortality of patients with breast cancer.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls).

Epigenetic silencing of RNF144A expression in breast cancer cells through promoter hypermethylation and MBD4.

Emerging evidence shows that ring finger protein 144A (RNF144A), a poorly characterized member of the Ring-between-Ring (RBR) family of E3 ubiquitin ligases, is a potential tumor suppressor gene. However, its regulatory mechanism in breast cancer remains undefined. Here, we report that RNF144A promoter contains a putative CpG island and the methylation levels of RNF144A promoter are higher in primary breast tumors than those in normal breast tissues.